Back to resultsTo Study the Effects of Aliskiren on Albuminuria and Various Biomarkers in Patients With Nephropathy (ARIA)
Primary Purpose
Non-diabetic Nephropathy
Status
Terminated
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Aliskiren
Placebo to Aliskiren
Hydrochlorothiazide (HCTZ)
Placebo to Hydrochlorothiazide (HCTZ)
Ramipril
Sponsored by
About this trial
This is an interventional treatment trial for Non-diabetic Nephropathy
Eligibility Criteria
Inclusion Criteria:
- Male and female subjects, age 18 years and above
- Patients with chronic kidney disease of non-diabetic origin
- Glomerular filtration rate >30 ml/min/1.73m2
- Patients with a history of hypertension and msSBP (mean systolic blood pressure) of <160 mm Hg and msDBP (mean diastolic blood pressure) <105 mm Hg at screening and baseline.
- Subjects must have a body mass index (BMI) within the range of 18 and 35 kg/m2
Exclusion Criteria:
- Previously treated (within 3 months of screening) with aliskiren or a combination of aliskiren and ramipril.
- Severe hypertension (msDBP ≥110 mmHg and msSBP ≥180 mmHg)
- Pregnant or nursing (lactating) women,
- A medical history of unstable coronary artery disease, myocardial infarction, coronary bypass surgery or cerebrovascular accident within the last six (6) months
- Diabetes mellitus, Heart failure
- High rate of renal function loss
- History of severe hypersensitivity or contraindications to any of the medications or drugs belonging to the similar therapeutic class as the study drugs and the excipients.
- History of liver disease, positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
- History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
Other protocol-defined inclusion/exclusion criteria applied
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)+HCTZ/Ram+Ali/Ram
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)/Ram+Ali + HCTZ/Ram
Arm Description
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d. Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule HCTZ 25 mg o.d. Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d. Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d. Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule placebo to HCTZ 25 mg o.d. Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule HCTZ 25 mg o.d. Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Outcomes
Primary Outcome Measures
Effect of Aliskiren on Albuminuria as Measured by Urinary Albumin Excretion Rate (UAER)
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
Effect of Aliskiren on Albuminuria as Measured by Creatinine Indexed Albumin
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
Secondary Outcome Measures
Mean Sitting Systolic Blood Pressure (msSBP)
At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Systolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msSBP was calculated. All BP measurements were to be performed on the same arm.
Mean Sitting Diastolic Blood Pressure (msDBP)
At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Diastolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msDBP was calculated. All BP measurements were to be performed on the same arm.
Mean Glomerular Filtration Rate (GFR) as Measurement of Renal Function
All patients had to visit the main center for renal function measurements. The measurements were performed using the constant infusion method with I-iothalamate (IOT) and I-hippuran. GFR was calculated as the urinary clearance of IOT.
Mean Effective Renal Plasma Flow (ERPF) as One of Hemodynamic Assessments
Percentage of Renal Filtration Fraction (RFF) as One of Hemodynamic Assessments
Mean Extracellular Volume (ECV) as One of Hemodynamic Assessments
Plasma Rennin Activity (PRA)
Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. Plasma PRA is a direct measure of the formation of Ang I in the plasma.
Plasma Rennin Concentration (PRC)
Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. PRC measures the concentration of immunoactive renin in the plasma.
Number of Participants With Adverse Events, Serious Adverse Events and Death as Assessment of Safety and Tolerability of Aliskiren Added to Ramipril
Full Information
NCT ID
NCT01302899
First Posted
February 9, 2011
Last Updated
December 21, 2012
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01302899
Brief Title
To Study the Effects of Aliskiren on Albuminuria and Various Biomarkers in Patients With Nephropathy
Acronym
ARIA
Official Title
A Single-blind, Double Dummy, Randomized, Multi-dose, Two Sequence, Crossover, Study to Investigate the Effects of Renin Inhibitor (Aliskiren 300 mg) on Albuminuria in Non-diabetic Nephropathy Patients Treated With Ramipril 10 mg and Volume Intervention (ARIA)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Terminated
Why Stopped
In consequence of termination of ALTITUDE. A number of studies were continued in consultation with the Altitude Data Monitoring Committee.
Study Start Date
January 2011 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
The study is designed to primarily assess the effect of aliskiren on albuminuria in patients with non-diabetic nephropathy when treated with ramipril and volume intervention.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-diabetic Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)+HCTZ/Ram+Ali/Ram
Arm Type
Experimental
Arm Description
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Arm Title
Ramipril (Ram) +HCTZ/Ram+Aliskiren (Ali)/Ram+Ali + HCTZ/Ram
Arm Type
Experimental
Arm Description
Period 1(Day 1 to end of week 6): 1 tablet ramipril 10 mg once daily (o.d.) + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule Hydrochlorothiazide (HCTZ) 25 mg o.d.
Period 2 (Weeks 7 to 12): 1 tablet ramipril 10 mg o.d.+ 1 tablet aliskiren 150 mg in 1st week of period; thereafter, 2 tablets aliskiren 150mg o.d.+ 1 capsule placebo to HCTZ 25 mg o.d.
Period 3 (Weeks 13 to 18): 1 tablet ramipril 10 mg o.d. + 2 tablets aliskiren 150mg o.d. + 1 capsule HCTZ 25 mg o.d.
Period 4 (Weeks 19 to 26): 1 tablet ramipril 10 mg o.d. + 2 tablets placebo to aliskiren 150mg o.d. + 1 capsule placebo to HCTZ 25 mg o.d.
Intervention Type
Drug
Intervention Name(s)
Aliskiren
Intervention Description
Aliskiren 150 mg (Tablet)
Intervention Type
Drug
Intervention Name(s)
Placebo to Aliskiren
Intervention Description
Aliskiren 150 mg Matching Placebo (Tablet)
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide (HCTZ)
Intervention Description
HCTZ 25mg (Capsule)
Intervention Type
Drug
Intervention Name(s)
Placebo to Hydrochlorothiazide (HCTZ)
Intervention Description
HCTZ 25mg (Capsule) Matching Placebo
Intervention Type
Drug
Intervention Name(s)
Ramipril
Intervention Description
Ramipril 10mg (Tablet)
Primary Outcome Measure Information:
Title
Effect of Aliskiren on Albuminuria as Measured by Urinary Albumin Excretion Rate (UAER)
Description
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
Time Frame
26 weeks
Title
Effect of Aliskiren on Albuminuria as Measured by Creatinine Indexed Albumin
Description
Two 24-hour collections of urine were to be made at each study visit. The arithmetic mean of the two collections were planned to be used in the calculation of summary statistics and the statistical analyses.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Mean Sitting Systolic Blood Pressure (msSBP)
Description
At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Systolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msSBP was calculated. All BP measurements were to be performed on the same arm.
Time Frame
26 weeks
Title
Mean Sitting Diastolic Blood Pressure (msDBP)
Description
At study entry, blood pressure (BP) was measured in both arms. If there was a clinically relevant difference in readings between arms (≥ 10 mmHg in systolic BP and/or ≥ 5 mmHg in diastolic BP), the arm with higher BP reading was used. If there was no clinically significant difference between arms, the non-dominant arm was used through out study. Diastolic blood pressure were assessed after the patient rested quietly in the sitting position for at least 3 minutes. For each sitting assessment, blood pressure was assessed at least 3 times. From these assessments, msDBP was calculated. All BP measurements were to be performed on the same arm.
Time Frame
26 weeks
Title
Mean Glomerular Filtration Rate (GFR) as Measurement of Renal Function
Description
All patients had to visit the main center for renal function measurements. The measurements were performed using the constant infusion method with I-iothalamate (IOT) and I-hippuran. GFR was calculated as the urinary clearance of IOT.
Time Frame
26 weeks
Title
Mean Effective Renal Plasma Flow (ERPF) as One of Hemodynamic Assessments
Time Frame
26 weeks
Title
Percentage of Renal Filtration Fraction (RFF) as One of Hemodynamic Assessments
Time Frame
26 weeks
Title
Mean Extracellular Volume (ECV) as One of Hemodynamic Assessments
Time Frame
26 weeks
Title
Plasma Rennin Activity (PRA)
Description
Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. Plasma PRA is a direct measure of the formation of Ang I in the plasma.
Time Frame
Baseline to week 26
Title
Plasma Rennin Concentration (PRC)
Description
Blood biomarkers were obtained from blood samples in all patients at the time points such as baseline, week 6, week 12, week 18 and week 26. PRC measures the concentration of immunoactive renin in the plasma.
Time Frame
Baseline to week 26
Title
Number of Participants With Adverse Events, Serious Adverse Events and Death as Assessment of Safety and Tolerability of Aliskiren Added to Ramipril
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female subjects, age 18 years and above
Patients with chronic kidney disease of non-diabetic origin
Glomerular filtration rate >30 ml/min/1.73m2
Patients with a history of hypertension and msSBP (mean systolic blood pressure) of <160 mm Hg and msDBP (mean diastolic blood pressure) <105 mm Hg at screening and baseline.
Subjects must have a body mass index (BMI) within the range of 18 and 35 kg/m2
Exclusion Criteria:
Previously treated (within 3 months of screening) with aliskiren or a combination of aliskiren and ramipril.
Severe hypertension (msDBP ≥110 mmHg and msSBP ≥180 mmHg)
Pregnant or nursing (lactating) women,
A medical history of unstable coronary artery disease, myocardial infarction, coronary bypass surgery or cerebrovascular accident within the last six (6) months
Diabetes mellitus, Heart failure
High rate of renal function loss
History of severe hypersensitivity or contraindications to any of the medications or drugs belonging to the similar therapeutic class as the study drugs and the excipients.
History of liver disease, positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
Other protocol-defined inclusion/exclusion criteria applied
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Groningen
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Leeuwarden
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
To Study the Effects of Aliskiren on Albuminuria and Various Biomarkers in Patients With Nephropathy
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